SINEFUNGIN AND TAXOL EFFECTS ON CELL-CYCLE AND CYTOSKELETON OF LEISHMANIA-DONOVANI PROMASTIGOTES

Sinefungin is an antibiotic possessing a strong anti-leishmanial activ ity. Among the most important effects of this molecule on Leishmania d onovani promastigotes are morphological modifications and a very rapid and effective inhibition of DNA synthesis. These cells contain a sing le DNA-rich mitochondrion whose division cycle is coordinated with the nuclear division cycle. We have developed a flow-cytometric procedure based upon mithramycin as fluorochrome that can perform quantitative cell cycle analysis on the nuclear DNA. Cell cycle progression was ana lyzed to establish that sinefungin irreversibly blocks the promastigot es in early S phase. Sinefungin did not react with stationary cells as they were arrested in G1. Surprisingly, taxol, a microtubule-stabiliz ing drug, induced the same morphological modifications as sinefungin a lthough it interfered with the G2/M progression. According to immunofl uorescence studies, the stable microtubular network is apparently affe cted neither by taxol nor by sinefungin. (C) 1996 Academic Press, Inc.